Macrophages Repair Broken Capillaries in the Brain

Here researchers investigate how immune cells in the brain work to fix tiny breakages of blood vessels. The link between vascular aging and neurodegeneration is most likely largely driven by breakage of blood vessels in the brain. Increased stiffening of vessels and increased blood pressure causes an ever greater frequency of microbleeds, each a tiny unnoticed stroke in essence, destroying a small piece of brain tissue. Over time that destruction adds up. The ideal treatment is to periodically repair the damage that causes stiffness and other deterioration in blood vessels, such as cross-linking, calcification, and mechanisms of atherosclerosis involving oxidized lipids and macrophage behavior, thus preventing breakages. Enhancing repair of the blood vessels after the fact of breakage is probably also useful, though the damage to neural tissue may be done by that point.

As we age, tiny blood vessels in the brain stiffen and sometimes rupture, causing "microbleeds." This damage has been associated with neurodegenerative diseases and cognitive decline, but whether the brain can naturally repair itself beyond growing new blood-vessel tissue has been unknown. A zebrafish study now describes for the first time how white blood cells called macrophages can grab the broken ends of a blood vessel and stick them back together. "We believe that this macrophage behavior is the major cellular mechanism to repair ruptures of blood vessels and avoid microbleeding in the brain."

To simulate a human brain microbleed, researchers shot lasers into the brains of live zebrafish to rupture small blood vessels, creating a clean split in the tissue with two broken ends. Then, the researchers used a specialized microscope to watch what happened next. The repair process started about a half hour after the laser injury. A macrophage showed up at the damaged blood vessel site and extended two "arms" from its body toward the ends of the broken blood vessel, producing a variety of adhesion molecules to attach itself. Then, it pulled the two broken ends together to mediate their repair. The researchers suspect that adhesion molecules produced by the blood-vessel tissue also play a role in reattachment. Once they were adhered, the macrophage left the scene. The whole process took about three hours. "After we confirmed that the macrophage mediates this repair through direct physical adhesion and generation of mechanical traction forces, we were excited. This is a previously unexpected role of macrophages."

A similar repair process also occurred outside the brain. When the researchers ruptured a blood vessel in the zebrafish fin using a laser, a macrophage arrived at the injury site and extended its protrusions to pull the broken blood vessel back together. The researchers did observe a few quirks in the process. When they used a laser strike to destroy the first macrophage that arrived at a laser-wound site in the brain, no other macrophages came to help repair the breakage (but another macrophage arrived to eat the dead one). Rarely, two macrophages would arrive at the injury on their own, each grab a broken end of the blood vessel, and then simply disengage without fixing the damage. Macrophages aren't the brain's only repair mechanism for small broken blood vessels, though they look to be the fastest and most efficient.



I'm just going to throw this out there:
I have the theory that macrophages are responsible for *all* repair to bodily tissue damage.
I further posit that aging is in part a signaling problem: the macrophages need the correct signals to build up and need other signals to tear down.

I suspect that as we age something goes wrong with the signaling and the macrophages tend towards the "tear down" side of things instead of the "build up".

Posted by: xd at May 4th, 2016 2:50 PM

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